β‐Globin gene cluster haplotypes and HbF levels are not the only modulators of sickle cell disease in Lebanon

Abstract

Sickle cell disease (SCD) is an inherited autosomal recessive disorder of the beta-globin chain. Despite the fact that all subjects with SCD have the same single base pair mutation, the severity of the clinical and hematological manifestations is extremely variable. This study examined for the first time in Lebanon the correlation between the clinical manifestation of SCD and the beta-globin gene haplotypes. The haplotypes of 50 patients diagnosed with SCD were determined using polymerase chain reaction amplification of fragments containing nine polymorphic restriction sites around and within the epsilon-Ggamma-Agamma-psibeta-delta-beta-globin gene complex. Most reported haplotypes were found in our population with the Benin haplotype as the most prevalent one. When the patients were divided according to their HbF levels into three groups (Group A: HbF < 5%, Group B: HbF between 5 and 15%, and Group C: HbF > 15%), surprisingly, the highest levels of HbF were associated with the most severe clinical cases. Our findings suggest that fetal hemoglobin levels are important but not the only parameters that affect the severity of the disease. In addition, the high levels of HbF in patients with CAR haplotypes did not seem to ameliorate the severity of symptoms, suggesting that genetic factors other than haplotypes are the major determinants of increased HbF levels in Lebanon.

Clinical and molecular characteristics of sickle cell anemia in the northeast of Brazil

“…However, our results do not agree with some previous published data (Bunn and Forget, 1986;Costa et al, 1994;Lugo et al, 2003) on HbF levels and β S -globin gene haplotypes but are consistant with some other reports (Falusi and Kulozik, 1990;Mouele et al, 1999;Inati et al, 2003). In our study, the presence of high HbF levels for the CAR/CAR haplotype could be due to sequence variations in regulatory regions, such as the 5'HS2 and flanking region of the γ gene (Lanclos et al, 1991;Ofori-Acquah et al, 2001).…”

Sickle cell disease: reappraisal of the role of foetal haemoglobin levels in the frequency of vaso-occlusive crisis

“…15 For instance, in one report from Lebanon, high HbF concentration was associated with increased disease severity 16 , a finding which warrants further investigation.…”

&lt;i&gt;&#223;&lt;/i&gt;-Globin Gene Cluster Haplotypes and Clinical Severity in Sickle Cell Anemia Patients in Southern Brazil

“…Gonçalves et al [31] also observed a high HbF concentration in Bantu/Bantu individuals, who usually present average levels below 5% [35]. Also, in a study conducted in Lebanon, a higher HbF level was not considered a marker of low severity in SCA patients, as higher HbF levels were surprisingly associated with more severe clinical cases, suggesting that increased HbF levels and genetic factors other than haplotypes were the major determinants of SCA severity in that population [3]. HbF gene expression is regulated by elements linked to the β-globin gene complex that are associated with the β-globin gene haplotype, and by trans-acting elements associated with the BCL11A gene on chromosome 2p16 and the HBS1L-MYB intergenic region on chromosome 6q23 (Steinberg, 2013).…”

“…HbS polymerizes under low oxygen tension (hypoxia), producing the characteristic sickle-shaped erythrocytes [3]. This event leads to hemolysis that promotes adhesive properties of circulating cells and the vessel wall.…”